Design, synthesis, and inhibitory activity of hydroquinone ester derivatives against mushroom tyrosinase

doi:10.1039/d4ra00007b

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	Design, synthesis, and inhibitory activity of hydroquinone ester derivatives against mushroom tyrosinase
	Xie, Dong; Han, Kangjia; Jiang, Qian; Xie, Sida; Zhou, Jielong; Zhang, Yingjun; Xu, Junming; He, Yuanping; Zhao, Ping; Yang, Xiaoqin
	2024
发表期刊	RSC ADVANCES
卷号	14 期号:9 页码:6085-6095
摘要	Tyrosinase is a widely distributed copper-containing enzyme found in various organisms, playing a crucial role in the process of melanin production. Inhibiting its activity can reduce skin pigmentation. Hydroquinone is an efficient inhibitor of tyrosinase, but its safety has been a subject of debate. In this research, a scaffold hybridization strategy was employed to synthesize a series of hydroquinone-benzoyl ester analogs (3a-3g). The synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase (mTyr). The results revealed that these hydroquinone-benzoyl ester analogs exhibited inhibitory activity against mTyr, with compounds 3a-3e displaying higher activity, with compound 3b demonstrating the highest potency (IC50 = 0.18 +/- 0.06 mu M). Kinetic studies demonstrated that the inhibition of mTyr by compounds 3a-3e was reversible, although their inhibition mechanisms varied. Compounds 3a and 3c exhibited non-competitive inhibition, while 3b displayed mixed inhibition, and 3d and 3e showed competitive inhibition. UV spectroscopy analysis indicated that none of these compounds chelated with copper ions in the active center of the enzyme. Molecular docking simulations and molecular dynamics studies revealed that compounds 3a-3e could access the active pocket of mTyr and interact with amino acid residues in the active site. These interactions influenced the conformational flexibility of the receptor protein, subsequently affecting substrate-enzyme binding and reducing enzyme catalytic activity, in line with experimental findings. Furthermore, in vitro melanoma cytotoxicity assay of compound 3b demonstrated its higher toxicity to A375 cells, while displaying low toxicity to HaCaT cells, with a dose-dependent effect. These results provide a theoretical foundation and practical basis for the development of novel tyrosinase inhibitors.Tyrosinase is a widely distributed copper-containing enzyme found in various organisms, playing a crucial role in the process of melanin production.
DOI	10.1039/d4ra00007b
WOS记录号	WOS:001163256500001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75973
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Xie, Dong,Han, Kangjia,Jiang, Qian,et al. Design, synthesis, and inhibitory activity of hydroquinone ester derivatives against mushroom tyrosinase[J]. RSC ADVANCES,2024,14(9):6085-6095.
APA	Xie, Dong.,Han, Kangjia.,Jiang, Qian.,Xie, Sida.,Zhou, Jielong.,...&Yang, Xiaoqin.(2024).Design, synthesis, and inhibitory activity of hydroquinone ester derivatives against mushroom tyrosinase.RSC ADVANCES,14(9),6085-6095.
MLA	Xie, Dong,et al."Design, synthesis, and inhibitory activity of hydroquinone ester derivatives against mushroom tyrosinase".RSC ADVANCES 14.9(2024):6085-6095.

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